Physicians are increasingly confronting the difficult problem of management of patients with sepsis. A current debate in the field is the degree to which sepsis is primarily a disorder due to tissue injury from uncontrolled inflammation versus a disorder due to immunosuppression and failure to control invading pathogens. Recent evidence indicates that some patients with sepsis enter a prolonged anti-inflammatory immunosuppressive phase. This immunosuppressive phase is characterized by inability of the patient to clear their initial infection and development of secondary hospital-acquired infections. Another feature of sepsis consistent with impaired immunity is reactivation of latent viruses. The working hypothesis of the present proposal is that sepsis results in loss of immunity manifested by a variety of measures including decreased absolute lymphocyte counts, decreased CD4, CD8, and NK cell counts resulting in viral reactivation. At the conclusion of the project, a method to identify when patients enter the immunosuppressive phase of sepsis will have been identified and key factors that might contribute to sepsis pathogenesis will have been discovered. PUBLIC HEALTH RELEVANCE: In Layman Terms Sepsis is the systemic inflammatory response that occurs during severe infection. Sepsis causes approximately 220,000 deaths in the United States alone. Although sepsis typically starts as a condition with excessive inflammation, if it persists, patients develop a state of impaired immunity and immune suppression. The impaired immunity can manifest itself in many ways including infection with organisms that are not particularly virulent to healthy individuals with normal immune systems. This project seeks to relate the loss in patient immunity with other measures including decreased absolute lymphocyte counts and viral reactivation. We hope to determine methods that can be used to diagnose the stage of sepsis, i.e., whether the patient is in the excessive inflammatory phase or the impaired immunity phase.